A cDNA encoding the calcitonin gene-related peptide type 1 receptor

Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse biological effects including potent vasodilator activity. We report here the cloning of a complementary DNA (cDNA) encoding a human CGRP(1) receptor, which shares significant peptide sequence homology with the human calcitonin receptor, a member of the G-protein coupled receptor superfamily. Northern blot analysis revealed that the messenger RNA for this receptor is predominantly expressed in the lung and heart. In situ studies showed specific localization of the receptor mRNA to alveolar cells in the lung and to cardiac myocytes in the heart. Stable expression of the cDNA in human embryonic kidney 293 (HEK 293) cells produced specific, high affinity binding sites for CGRP that displayed pharmacological and functional properties very similar to native human CGRP(1) receptor. Exposure of these cells to CGRP resulted in a 60-fold increase in cAMP production, which was inhibited in a competitive manner by the CGRP(1) receptor antagonist, CGR9-(8-37).